During spinal cord injury (SCI), there is an extremely high release of the neurotransmitter glutamate. This leads to activation of glutamate NMDA (N-methyl-D-aspartate) receptors and to the production of reactive oxygen species (ROS) that have detrimental effects on the neurons, often resulting in neuronal death. Interestingly, interfering with the interactions between NMDA receptor and PSD-95 (postsynaptic density-95), a synaptic structural protein that enhances NMDA receptor surface expression and signaling efficiency, may have neuroprotective effects. Cypin (cytosolic protein interacting with PSD-95) is a major binding partner of PSD-95. PSD-95 belongs to a family of proteins called MAGUK (membrane-associate guanylate kinase), involved with the recruitment of signaling molecules to the synapse. Therefore, PSD-95 and cypin play crucial roles in the clustering of molecules that respond to neurotransmitters at the synaptic site. Thus, with previous data from the Firestein laboratory showing that overexpression of cypin may indirectly downregulate the signaling strength of NMDA receptors, we sought to investigate the role of cypin in limiting damaging effects of SCI. For this purpose, we analyzed the effect of cypin overexpression on PSD-95 distribution in spinal cord neurons and the neuroprotective role of cypin overexpression in these neurons after glutamate-induced toxicity. Here we show that overexpression of cypin does decrease the number of PSD-95 clusters in cultured spinal cord neurons. However, in our experimental conditions, we did not find that the overexpression of cypin significantly improves neuronal survival.